Exendin‐4‐based imaging in insulinoma localization: Systematic review and meta‐analysis

Abstract Background and context Glucagon‑like peptide‑1 receptor (GLP‐1 R) based imaging has shown higher sensitivity for insulinoma localization as compared to other anatomic/functional imaging. Methodology We reviewed the published English literature for GLP‐1 R targeted imaging in insulinoma in PubMed until August 2020 in accordance with PRISMA guidelines using the MeSH terms “((Exendin‐4 PET/CT) OR (Exendin‐4 SPECT/CT) OR (GLP‐1 R imaging)) AND (Insulinoma)”. An individual patient data‐metanalysis (IPD‐MA) was performed, and performance parameters were calculated for the histopathological diagnosis of insulinoma. Main outcome measures True‐positive (TP), false‐positive (FP), false‐negative (FN), true‐negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for insulinoma localization. Results A total of 179 cases (316 lesions) from 16 publications were included for IPD‐MA. For insulinoma localization, exendin‐4‐PET/CT (Sn & PPV: 94%) performed better than exendin‐4‐SPECT/CT (Sn: 63%, PPV: 94%). The Sn was lower in malignant insulinoma cases whereas the Sp was higher in cases with MEN‐1 syndrome. With exendin‐4‐based imaging, FP uptakes in Brunner’s gland, normal pancreas, and other β‐cell pathologies and FN results in pancreatic tail lesions and malignancy were seen in a few patients. TN results suggested the correct diagnosis of other endogenous hyperinsulinemic hypoglycaemia (EHH) subtypes. Conclusion For insulinoma localization, exendin‐4 PET/CT should be preferred over exendin‐4 SPECT/CT because of higher sensitivity and specificity. FP uptakes in Brunner’s gland, normal pancreas, and other β‐cell pathologies and FN results in tail lesions, and malignant insulinomas are limitations. Higher specificity for insulinoma localization is particularly useful in patients with MEN‐1 syndrome.